JP2001114675A - Vitamin composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily provide a stable excellent vitamin K composition. SOLUTION: This vitamin composition contains vitamin K and a flavonoid compound. Especially, the vitamin composition contains 1 pt.wt. of the vitamin K and 30 to 50,000 pts.wt. of the flavonoid compound. The flavonoid compound is selected from quercetin, rutin, hesperidin, hesperitin, myricetin, quercitrin, fisetin, apigenin, kaempferol, luteolin, eriocitrin, chalcone, anthocyanidin, leucoanthocyanidin, catechin, epicatechin, gallocatechin, epicatechin gallate, epigallocatechin gallate, and isoflavene. The vitamin composition preferably further contains a (bi)carbonate, a hydroxide, shell powder, petrified sea alga powder, coral powder or dolomite powder as an alkaline raw material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a vitamin composition having excellent stability.

[0002]

2. Description of the Related Art With the aging society, people have a strong interest in health. In particular, in osteoporosis, a decrease in bone density due to aging causes a fracture, skewing of the skeleton, etc., and the accompanying pain not only causes a decrease in quality of life (QOL), but in the worst case, for example, a femoral fracture You will be forced to live a bedridden lifestyle. Therefore, there is an increasing demand for effective means for suppressing a decrease in bone density and for preventing osteoporosis in order to increase QOL in old age.

[0003] Vitamin K, vitamin D ₃ , estrogens, isoflavones, ipriflavones, calcitonin, bisphosphonates, trehalose and the like are known to be expected to be effective in the prevention and treatment of osteoporosis. In particular, as a nutritional component contained in foods, it has been revealed that vitamin K has a function for bone, that is, a very important function for bone remolding. In the field of foods called functional foods, health foods, and dietary supplements, methods of using single components or composite components aimed at synergistic effects are also being studied.

[0004] Vitamin K is a 1,4-naphthoquinone skeleton with an isoprene derivative side chain attached thereto. Vitamin K ₁ (phyloquinone) produced by plants, vitamin K ₂ (menaquinone) produced by bacteria, and synthetic products There is vitamin K ₃ (menadione). Menaquinone is classified into MK1 to MK14 according to the number of isoprene units.

[0005] In foods and pharmaceuticals, the properties of vitamin K are unstable to light and alkali. Therefore, when vitamin K is fortified, the stability of vitamin K is a problem. In particular, as a food for preventing osteoporosis, a combination of calcium and vitamin K is known, but sodium, potassium, magnesium, ammonium or other carbonates, bicarbonates, hydroxides, etc., or calcium carbonate as a main component Flour, coral powder, dolomite powder,
It is known that the stability of a material such as petrified seaweed powder or an alkaline material such as a material containing calcium oxide as a main component such as baked shell powder becomes worse when combined with vitamin K.

[0006] As a conventional countermeasure, for example, in the case of processing tablets, only vitamin K is double-dispersed with an excipient such as cellulose and then mixed with granules of an alkaline material and other excipients. There is a method of tableting (food and development, vol34, N
o. 4, P40-42), but the stability of vitamin K over time has not been sufficiently resolved.

In general, a lipid film is heated and dissolved in an organic solvent, and the solution is spray-dried on the surface of the main component, or a fat film method using no organic solvent (Japanese Patent No. 1479697, Japanese Patent Publication No. 3-58264, Patent No. 2729
No. 494) and microcapsules (Patent No. 1002105)
It is also conceivable to apply vitamin K to a film and stabilize it by applying such techniques.

[0008] However, the fat and oil coating method using an organic solvent employs a generally used organic solvent such as a halogenated hydrocarbon such as carbon tetrachloride or chloroform, hexane, or the like.
Hydrocarbons such as benzene, lower alcohols, acetone and the like require a great deal of time to completely dry and remove them. In addition, if a flammable solvent with low toxicity is used, explosion-proof equipment will be required for disaster prevention.
For highly toxic organic solvents such as hydrocarbons and halogenated hydrocarbons, to prevent leakage to the working environment during production and to maintain the safety and health of workers, or to prevent environmental pollution due to evaporated and exhausted organic solvents. In order to achieve this, there are a number of problems such as a large capital investment.

On the other hand, a method for producing a sustained-release preparation provided as a method without using an organic solvent (Japanese Patent No. 1479697, Japanese Patent Publication No. 3-58264, Japanese Patent No. 2729494), and a method for producing microcapsules ( Patent No. 1002105)
As the lipid substances used, higher alcohols, higher fatty acids, higher fatty acid glycerin esters,
Hardened oils, waxes, hydrocarbons and the like can be mentioned.For example, hardened oil has been suggested to be associated with the risk of cardiovascular disease in Europe and the United States. Is not appropriate to use. Furthermore, each lipid substance used must be mixed under a temperature condition not lower than its melting point, and vitamin K ₁ (phyloquinone) having a melting point of −20 ° C. and vitamin K ₂ (menaquinone) having a melting point of 54 ° C. With regard to ()), these technologies have not been sufficiently commercialized.

As a coating method other than the oil film, a method using a cellulose derivative, a natural polysaccharide, zein, gelatin or the like, and a microcapsule using gelatin or the like are also known. In addition to the high cost of equipment investment, the time required for drying, and the increase in the number of manufacturing processes, the cost is increased. Alternatively, there is a problem that the cost is increased when the food is used for the purpose of nutritional enhancement.

[0011]

Vitamin K is relatively stable to heat, air oxidation and dilute acid, but unstable to light. Further, since it is very unstable to alkali, its stability becomes a problem when processed into foods and pharmaceuticals, especially when combined with alkaline materials. An object of the present invention is to eliminate these disadvantages and to provide a vitamin K composition having excellent stability.

[0012]

Means for Solving the Problems The present inventors have found that the stability of vitamin K can be improved by adding flavonoids to vitamin K, and have reached the present invention.
That is, the present invention is a vitamin composition containing vitamin K and flavonoids.

In the present invention, the mixing ratio of vitamin K and flavonoids is preferably 30 to 50,000 parts by mass, more preferably 50 to 50,000 parts by mass of flavonoids per 1 part by mass of vitamin K.
Not more than 100 parts by mass, particularly preferably not less than 100 parts by mass and 50,0 parts by mass.
The amount is not more than 00 parts by mass, and a particularly stable vitamin K composition can be obtained in this range. When the compounding ratio of the flavonoids to 1 part by mass of vitamin K is less than 30 parts by mass, the effect of the present invention is weakened particularly in combination with an alkaline material such as a calcium or magnesium material containing carbonate as a main component. On the other hand, when the compounding ratio of the flavonoids exceeds 50,000 parts by mass, bitterness, astringency and the like derived from the flavonoids appear strongly.

Vitamin K in the present invention means vitamin K
_One or two selected from ₁ (phyloquinone), vitamin K ₂ (menaquinone), and vitamin K ₃ (menadione)
Any of a mixture of more than one kind may be used, and the effect of the present invention does not change regardless of whether natural or synthetic vitamin K is used. The preparation of specific vitamin K, such as vitamin K ₁ is subjected to extraction with an organic solvent from the green and yellow vegetables, soybean, which or extract of, or its starch, dextrin, zein etc. excipients, adsorbent And pulverizing by an appropriate means. Vitamin K ₂ is mainly produced by a fermentation method using a microorganism, for example, a method of culturing Brevibacterium and extracting and purifying the produced vitamin K ₂ , or a deodorizing distillation by-produced in a step of purifying vegetable oils and fats. There is a method in which the product is extracted with an organic solvent and then purified. In the synthesis method, reduced vitamin K is used as a starting material, which is dissolved in an organic solvent such as isopropyl ether, an alkali aqueous solution adjusted with alkali and water is added, and oxygen is introduced under stirring to carry out the reaction. A method for obtaining vitamin K is known.

The flavonoids used in the present invention are a kind of phenols, and basically have a flavone or flavanone skeleton, isoflavone skeleton or the like having a C ₆ -C ₃ -C ₆ structure. Specific examples include quercetin, rutin, hesperidin, hesperitin, myricetin, quercitrin, fisetin, apigenin, kaempferol, luteolin, eriocitrin, chalcone,
Anthocyanidin, leucoanthocyanidin, catechin, epicatechin, gallocatechin, epigallocatechin,
Epicatechin gallate, epigallocatechin gallate, isoflavone and the like. Further, those used as flavonoids may be aglycone or glycoside, or those produced by enzymatic treatment or other methods. These may be used alone or in combination of two or more. Hereinafter, typical flavonoids will be described, but the present invention is not limited thereto.

For example, isoflavones include glycitin,
genistin, daidzin, glycitein, genistein, daidzei
n, 6 "-O-acetyldaidzin, 6" -O-malonyldaidzin, 6 "-
O-acetylglycitin, 6 "-O-malonylglycitin, 6" -O-ace
tylgenistin, 6 ”-O-maronylgenistin, Biochanin A (me
thoxygenistein), Formononetin (methoxydaidzein), etc.
In addition, those which have undergone some modification such as succinylation and hydroxylation by microbial fermentation, for example, succinylated daidzin, glycitin, gen
istin and the like, or those modified by enzymatic treatment or other methods.

As a general isoflavone material, it is preferable to contain at least 0.1% by mass or more in terms of the total amount of isoflavones. For example, soybean, soybean hypocotyl, red clover, kudzu, etc. containing a large amount of isoflavones are dried as they are, What was crushed, or separated from them through an extraction step, purified, or soybeans and soybean hypocotyls, red clover, kudzu, etc., dried and crushed, microorganisms, such as natto or black koji or red koji, There are powders obtained by fermentation with a koji mold such as Aspergillus oryzae by appropriate means, or powders obtained by separating and purifying them through an extraction step or the like.

Hesperidin and rutin are also called vitamin P. In general, hesperidin is obtained by extracting and purifying water or an organic solvent such as ethanol from citrus peels, juices and seeds such as Unshu mandarin orange and grapefruit. On the other hand, rutin is extracted and purified with water, ethanol or the like from the whole plant of the genus buckwheat or the flowers and buds of the leguminosaceae, or the whole plant of the leguminous red bean. In addition, hesperidin and rutin may be obtained by modifying the solution by enzymatic treatment or other methods, and water-soluble hesperidin or water-soluble rutin may be used. Further, hesperidin may be citrus peel and / or seed, and rutin may be buckwheat. Fruits and / or buckwheat leaves may be ground and powdered.

The catechin is obtained, for example, by dry-distilling from the xylem of the legume peguasinium or the leaves of the camellia tea and extracting and purifying it with water or ethanol, and removing caffeine if necessary. May be used. In addition, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, and the like may be used, and these may be used alone or in combination of two or more.

In the present invention, when an alkaline material is contained, the effect can be more remarkably exhibited.
Alkaline materials include, for example, sodium, potassium,
Carbonates such as magnesium or ammonium, bicarbonates or hydroxides, scallops containing calcium carbonate as a main component, edible shell powder derived from oysters, petrified seaweed powder, coral powder, dolomite powder, etc. or baked shell powder. Such as those containing calcium oxide as a main component. The amount is not limited, and is, for example, preferably 0.05 to 50,000 parts by mass, more preferably 0.5 to 25,000 parts by mass, particularly preferably 2 parts by mass with respect to 1 part by mass of flavonoids. 0.5 to 22,500 parts by mass is preferred. Within this range, the stability of vitamin K is particularly well maintained. When the amount of the alkaline material is less than 0.05 parts by mass, it is generally difficult to uniformly disperse the alkaline material, which has a high specific gravity and easily aggregates, during mixing. If the amount exceeds 50,000 parts by mass, the effect of the present invention tends to be weak.

In the present invention, it is essential to contain vitamin K and flavonoids. In addition to these, if necessary, antioxidants such as vitamin E, sesame extract, tannins, phenols and the like Ingredients effective as antioxidants, food additives, pharmaceutically acceptable ingredients, pharmaceuticals, lactose, maltose, glucose used in food,
It may contain excipients such as sucrose, reduced maltose, reduced lactose, trehalose, erythritol, xylitol, sorbitol, mannitol, cellulose, starch, cellulose derivatives, dextrin, etc., adsorbents, coloring agents, flavors and the like.

The vitamin composition of the present invention is obtained by mixing vitamin K with flavonoids and other additives as required, or a mixed powder thereof, for example, by stirring granulation, fluidized bed granulation, extrusion molding. It can be easily obtained by granulating by means such as a wet granulation method typified by granules or other dry granulation methods. Further, these mixed powders or granule powders can be processed into tablets, hard capsules, soft capsules and the like as they are.

[0023]

EXAMPLES The effects of the present invention will be described below with reference to specific examples, but the present invention is not limited to these examples. The evaluation method is as follows. (1) Accelerated test For each Example and Comparative Example, the processed granules and tablets were filled in a light-shielding aluminum bag under the conditions of 40 ° C. and 75% RH. Then, an acceleration test was performed for three months, and the amount of vitamin K was measured. (2) Long-term storage test The vitamin K concentration of Example 7 and Comparative Examples 4 and 5 was measured when stored at room temperature for 3 months and 1 year in a light-shielding aluminum bag.

[0024] Examples 1-6, Comparative Examples 1 to 3 Vitamin K ₁ was used are ethanol extracted extract powder from celery, vitamin K ₂ used was extracted purified by fermentation. As the flavonoids, isoflavones, hesperidin and green tea catechin were selected and used. As the isoflavone, an extract powder extracted and purified from a powdered fermented product obtained by fermenting soybean with black koji mold and an extract powder extracted and purified from soybean hypocotyl were used. As hesperidin, a product of Alps Pharmaceutical Co., Ltd. was used. As the catechin, Sanphenon 100S and Sankatol of Taiyo Chemical Co., Ltd. were used. In each example and comparative example, Table 1
After mixing the respective ingredients based on the formulation of the above, a 70% aqueous ethanol solution is sprayed to perform stirring granulation, and the mixture is mixed with 50% ethanol.
C., vacuum dried for 3 hours, sized and granulated, and used as it was. Table 2 shows the results of storage by the accelerated test in terms of the residual ratio. Examples 1 to 6 in which flavonoids such as isoflavone, catechin, and hesperidin were added to vitamin K.
, Good stability was obtained.

[0025]

[Table 1]

[0026]

[Table 2]

Examples 7 to 8 and Comparative Example 5 Based on the formulation shown in Table 3, granulation was carried out in the same manner as in Example 1, and this was processed into tablets. The results of the accelerated test and the long-term storage test are shown in Table 4 as residual rates. In Examples 7 and 8, 3
Both conditions showed better stability than Comparative Example 4. Although Example 8 having a small content of flavonoids contains isoflavones, the residual rate after one year is lower than that of Example 7, and the stability is clearly superior to Comparative Example 4, The effect of the present invention tended to be somewhat weak.

[0028]

[Table 3]

[0029]

[Table 4]

[0030]

As described above, according to the present invention, after processing vitamin K, the problem of stability caused by combination with an alkaline material was solved, and a vitamin composition having excellent stability could be obtained.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 35/56 A61K 35/56 35/78 35/78 J CKE 47/00 47/00 47/02 47/02 47/08 47/08 47/22 47/22 47/26 47/26 A61P 3/02 109 A61P 3/02 109 19/10 19/10 F term (reference) 4B018 MD02 MD03 MD04 MD23 MD60 MD75 MD94 ME05 4C076 BB01 CC22 DD25Q DD28Q DD30Q DD40Q DD59Q DD69Q FF36 FF63 4C087 AA10 BA02 BB04 BB16 MA02 MA05 MA52 NA03 ZA97 ZC29 4C088 AA12 AB43 AB45 AB59 AB61 AB62 AC04 AC05 BA08 MA03 MA53 NA03 ZA97 ZA29 ZC29A29

Claims (10)

[Claims] 1. A vitamin composition comprising vitamin K and flavonoids. 2. The vitamin composition according to claim 1, wherein the flavonoids are contained in an amount of 30 to 50,000 parts by mass based on 1 part by mass of vitamin K. 3. The flavonoids are quercetin, rutin, hesperidin, hesperitin, myricetin, quercitrin, fisetin, apigenin, kaempferol, luteolin, eriocitrin, chalcone, anthocyanidin, leucoantocyanidin, catechin, epicatechin, gallocatechin, epigallocatechin. The vitamin composition according to claim 1 or 2, wherein the vitamin composition is at least one selected from the group consisting of epicatechin gallate, epigallocatechin gallate, and isoflavone. 4. A soybean, a soybean hypocotyl, a fermented soybean, a fermented soybean hypocotyl, a red clover, a kudzu, or a soybean extract, a soybean hypocotyl extract, a fermented soybean extract, or a soybean isoflavone extracted therefrom. The vitamin composition according to claim 3, wherein the vitamin composition is contained as one or more selected from a hypocotyl fermented extract, a red clover extract, and a kudzu extract. 5. The vitamin composition according to claim 3, wherein catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate or epigallocatechin gallate is contained as tea powder or tea extract. . 6. The method according to claim 3, wherein the catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate or epigallocatechin gallate is obtained by dry-distilling and extracting from the xylem of the legume peguasenyak. Vitamin composition. 7. Hesperidin is a citrus juice, pericarp,
The vitamin composition according to claim 3, which is contained as a seed or an extract of each of them. 8. The method according to claim 3, wherein the rutin is contained as buckwheat nuts, leaves, or extracts thereof.
The vitamin composition as described. 9. The vitamin composition according to claim 1, further comprising an alkaline material. 10. The powder according to claim 9, wherein the alkaline material is sodium, potassium, magnesium or ammonium carbonate, bicarbonate or hydroxide, edible shell powder, petrified seaweed powder, coral powder, dolomite powder or baked shell powder. Vitamin composition.